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  • Original Article
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A variant near the interleukin-6 gene is associated with fat mass in Caucasian men

Abstract

Context:

Regulation of fat mass appears to be associated with immune functions. Studies of knockout mice show that endogenous interleukin (IL)-6 can suppress mature-onset obesity.

Objective:

To systematically investigate associations of single nucleotide polymorphisms (SNPs) near the IL-6 (IL6) and IL-6 receptor (IL6R) genes with body fat mass, in support for our hypothesis that variants of these genes can be associated with obesity.

Design and Study Subjects:

The Gothenburg Osteoporosis and Obesity Determinants (GOOD) study is a population-based cross-sectional study of 18- to 20-year-old men (n=1049), from the Gothenburg area (Sweden). Major findings were confirmed in two additional cohorts consisting of elderly men from the Osteoporotic Fractures in Men (MrOS) Sweden (n=2851) and MrOS US (n=5611) multicenter population-based studies.

Main Outcome:

The genotype distributions and their association with fat mass in different compartments, measured with dual-energy X-ray absorptiometry.

Results:

Out of 18 evaluated tag SNPs near the IL6 and IL6R genes, a recently identified SNP rs10242595 G/A (minor allele frequency=29%) 3′ of the IL6 gene was negatively associated with the primary outcome total body fat mass (effect size −0.11 standard deviation (s.d.) units per A allele, P=0.02). This negative association with fat mass was also confirmed in the combined MrOS Sweden and MrOS US cohorts (effect size −0.05 s.d. units per A allele, P=0.002). When all three cohorts were combined (n=8927, Caucasian subjects), rs10242595*A showed a negative association with total body fat mass (effect size −0.05 s.d. units per A allele, P<0.0002). Furthermore, the rs10242595*A was associated with low body mass index (effect size −0.03, P<0.001) and smaller regional fat masses. None of the other SNPs investigated in the GOOD study were reproducibly associated with body fat.

Conclusions:

The IL6 gene polymorphism rs10242595*A is associated with decreased fat mass in three combined cohorts of 8927 Caucasian men.

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Acknowledgements

This work was supported by Swedish Research Council (no. K2007-54X-09894-16-3), EC FP6 funding (contract no. LSHM-CT-2003-503041), Johan och Jakob Söderbergs Foundation, Marcus Borgströms Foundation, Nilsson-Ehle Foundation, NovoNordisk Foundation, Swedish Medical Society, Swedish Society for Medical Research and Sahlgrenska Center for Cardiovascular and Metabolic Research (CMR, no. A305:188) which is supported by the Swedish Strategic Foundation. The MrOS US study was supported, in part, by Grants R01-AR049747 from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS). The Osteoporotic Fractures in Men Study was supported by the National Institutes of Health (NIH) funding. The following Institutes provide support: the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), the National Institute on Aging (NIA), the National Center for Research Resources (NCRR) and NIH Roadmap for Medical Research under the following grant numbers: U01 AR45580, U01 AR45614, U01 AR45632, U01 AR45647, U01 AR45654, U01 AR45583, U01 AG18197, U01 AG027810, UL1 RR024140, AR052000 and AR048841.

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Andersson, N., Strandberg, L., Nilsson, S. et al. A variant near the interleukin-6 gene is associated with fat mass in Caucasian men. Int J Obes 34, 1011–1019 (2010). https://doi.org/10.1038/ijo.2010.27

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